The disclosed subject matter relates to the detection of single-molecules. There is demand for DNA sequencing systems to be single-molecule, massively parallel, and real-time. For single-molecule optical techniques, however, the signal from a single fluorophore can be <2500 photons/sec (equivalent to electrical current levels on the order of 50 fA). This can lead to complex optics to try to collect every photon emitted and makes scaling of the platforms difficult. Conversely, relevant chemical reactions can be intentionally slowed to 1 Hz (or slower) to allow sufficient imaging times for these weak, noisy optical signals.
In contrast, electrochemical detection approaches, can have significantly higher signal levels (often several orders of magnitude stronger), allowing for high-bandwidth detection with the appropriate co-design of transducer, detector, and amplifier. Nanopore technology is one potential bioelectronic transduction mechanism. Nanopores, however, can be limited by the relatively short time biomolecules spend in the charge-sensitive region of the pore. Restricted by the use of off-the-shelf electronics, the noise-limited bandwidth of nanopore measurements is typically less than 100 kHz, limiting the available sensing and actuation strategies and defying multiplexed integration which would be required for any sequencing application.